New Clues About How Healthy Circuits Form in Developing Brains

New Clues About How Healthy Circuits Form in Developing Brains

Posted: March 17, 2015

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Scientists have a new understanding of how cells called interneurons embed themselves in neural networks as the brain develops. Interneurons form essential connections to keep those networks communicating while they perform their primary function, which is to encode and store information.

Reliably transmitting information requires tremendous coordination among the neurons in the brain, and cells that receive sensory information and trigger motor activity can’t do it on their own. Groups of interneurons are dedicated to overseeing the activity of neural networks, making sure cells keep pace with one another and stay in sync as they fire their impulses. Increasingly, scientists are recognizing that malfunction of interneurons can contribute to epilepsy, Alzheimer’s disease, schizophrenia, and other mental health conditions.

In work published online March 5th in the journal Neuron, a team of scientists (including 2014 NARSAD Distinguished Investigator grantee Paul Worley, M.D., at the Johns Hopkins School of Medicine) studied the development of an interneuron type in the brain’s hippocampus known as parvalbumin-expressing fast-spiking interneurons (PVFSIs). PVFSIs regulate neural circuits involved in navigation and memory. Disrupting their integration into these circuits can skew signaling and promote epilepsy or Alzheimer’s disease.

The team found that a pair of proteins called pentraxins––abbreviated NPTX2 and NPTXR––are essential for integrating PVFSIs into neural networks because they prepare proteins on the cells’ surfaces to attract connecting neurons. These proteins are secreted by excitatory nerve cells at synapses where connections are forged with PVFSIs. Secreted NPTXs bind glutamate receptors and control the strength of the connections. One of the pentraxins, NPTX2, is regulated in excitatory neurons by activity that is known to be important for correct wiring of the brain.

In mice without NPTX2 and NPTXR, interneurons in the developing brain form their connections later than usual. As a result, the circuits fail to establish the appropriate signaling rhythms later in life. The researchers found that mice with these circuit problems exhibited behaviors suggesting increased anxiety and impaired short-term memory compared to animals with functional pentraxins.

The essential role of NPTX2 and NPTXR in integrating PVFSIs into neural circuits makes them potential targets for treatments for disorders that involve imbalances in brain activity such as those associated with schizophrenia, the scientists say.

Read the abstract.